WASHINGTON, DC—Capillary whole blood or plasma spots can be used effectively for the analysis of antiepileptic drug (AED) levels, according to researchers at MEDTOX^® Laboratories in St. Paul. "The spots provide sufficient specimen for routine analysis, and the methodology has the sensitivity, linearity, reproducibility, and accuracy required for effective monitoring of these drug levels," said Jennifer A. Collins, PhD, laboratory director at MEDTOX and lead author of the study.

Traditionally, quantitative levels of anticonvulsants have been measured by serum or plasma prepared from whole blood collected by venipuncture, explained Dr. Collins—a process involving an appropriate collection facility, trained phlebotomists, special specimen-separation protocols, and frequently, transportation of the sample to a qualified laboratory for analysis. "While this protocol is achievable for many patients, individuals living in remote areas or individuals [such as geriatric or pediatric patients] who have difficulty providing samples may have more obstacles to overcome to ensure compliance with treatment/monitoring regimens," she said.

"Utilization of capillary blood samples collected onto filter paper eliminates the need for phlebotomy, allowing samples to be obtained by relatively untrained caregivers or patients," she continued. In addition to facilitating sample collection and analysis, this method "provides a means for caregivers to collect therapeutic drug-monitoring samples at crucial time points"—that is, proximate to a seizure or adverse drug reaction—thereby lessening what is sometimes a significant delay between such occurrences and the time of blood sampling and allowing for more accurate recording of drug levels during the adverse events.

Therefore, Dr. Collins and colleagues tried to determine whether capillary whole blood and plasma samples on filter paper provided an equivalent reading of anticonvulsant concentrations to those taken from venous whole blood or plasma. The preliminary findings were reported at the 2005 Joint Annual Meeting of the American Epilepsy Society and the American Clinical Neurophysiology Society.

THE PRICK OR THE PUNCTURE?

Study participants adhered to a monitoring schedule prescribed by treating physicians. Venipuncture samples of whole blood and plasma were compared to capillary samples taken by pricking the finger with a lancet. All samples were analyzed using high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. The assay included 13 AEDs: carbamazepine, carbamazepine-10,11-epoxide, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine monohydroxy derivative, phenobarbital, phenytoin, topiramate, valproic acid, and zonisamide. The venous plasma samples were considered predicate for comparison purposes, Dr. Collins said.

GOOD CORRELATION

Of the 28 sets of AED samples collected to date, 11 lamotrigine and nine levetiracetam sets have been completed (see Tables 1 and 2). "Preliminary data on the comparison of drug levels obtained from capillary blood or plasma spots on filter paper to drug levels obtained from venous plasma indicate good correlation for both lamotrigine and levetiracetam for all sample types," the investigators reported.

TIMELY RESULTS

"The collection of capillary blood spots on filter paper is minimally invasive, easy to perform, and temporally relevant," Dr. Collins said. It provides "a comprehensive, quantitative, precise analysis of commonly prescribed anticonvulsants across typical therapeutic ranges."

Importantly, "the ability of patients and caregivers to collect capillary samples in close proximity to an ictal or a toxic event without the need to procure phlebotomy services not only reduces patient perceived inconvenience of performing therapeutic drug monitoring testing but also increases the amount of useful information obtained by providing the physician with precise drug levels at time points most critical to managing an individual’s epilepsy," she added.

NR

—C. Justin Romano

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